Little is known about the signal transduction pathways controlling skin architecture and hair development, although these processes are likely to be very important for the understanding of mechanisms that are disturbed in human skin diseases such as psoriasis. We propose to investigate these questions using a mouse model called waved 3 (wa3). This spontaneous recessive mutation is characterized by wavy fur and open eyes (unfused eyelids) at birth. This phenotype is similar to that previously described for the mouse mutants waved 1 (wa1) and waved 2 (wa2), which respectively represent molecular defects in the growth factor TGF-alpha and in its receptor, EGFR. We have determined that wa3 maps to mouse chromosome 7, and is not allelic with wa1 or wa2. We propose to use a positional cloning approach in order to determine the molecular basis of the wa3 mutation, which will facilitate the analysis of its role in normal skin development as well as in skin diseases. We also propose to use genetic crosses of the wa3 mutant with transgenic mice that overexpress TGF-alpha in order to directly test the possibility that the wa3 product is required for normal expression of this growth factor.